Objective To examine the effect of the demethylating agent 5-aza-2’-deoxycytidine (5-AzaCdR)on pericyte-myofibroblast transition (PMT)in primary rat renal myofibroblasts. Methods Rat primary renal myofibroblasts were treated with 5-Aza-CdR 250 ng/mL for 72 h, and the degree of Epo promoter methylation was detected by pyrosequencing. Protein expression levels of α-smooth muscle actin (α-SMA), platelet-derived growth factor receptor-β (PDGFRβ)and DNA methyltransferase (Dnmt3a)were detected by immunofluorescence and Western blot, and erythropoietin (EPO)levels in the supernatant were detected. Results Compared with the control group, 5-Aza-CdR treatment significantly decreased the expression of Dnmt3a and hypermethylation of the Epo promoter, and subsequently decreased the expression of α-SMA and the expression ratio of α-SMA to PDGFRβ in myofibroblasts. Meanwhile, 5-Aza-CdR treatment increased the level of EPO in the cell supernatant. Conclusions 5-Aza-CdR can reverse PMT by inhibiting Epo promoter hypermethylation in primary renal myofibroblasts.